ArticlesIncreased Expression of Tumor Necrosis Factor-α in Diabetic Macrovasculopathy
Section snippets
Patients
This prospective controlled clinical study was conducted at Hospital de Clı́nicas de Porto Alegre (a tertiary care center) between April and October 1996. During this period, all vessel segments obtained from both type 2 diabetic and nondiabetic patients submitted to inferior limb amputation for chronic atherosclerotic disease without clinical and laboratorial evidence of gangrene were studied. Type 2 diabetes mellitus was defined according to World Health Organization criteria (16). Exclusion
Patients
Clinical and laboratory characteristics of type 2 diabetic and nondiabetic patients are described in Table 1. There was an increased number of smoking patients in the nondiabetic group (87%) compared with type 2 diabetic patients (40%) (p < 0.05). Also, diabetic patients had higher plasma glucose levels than the control group (p < 0.05). The known duration of diabetes in this group was 19.5 ± 8.8 years, their treatment being diet only (n = 5), insulin (n = 7) and hypoglycemic agents (n = 8).
Histological Analysis
Discussion
In the present study, we characterized increased expression of an immunoinflammatory mediator, TNF-α, in atherosclerotic lesions from type 2 diabetic compared with atherosclerotic lesions from nondiabetic patients. To our knowledge, this is the first report to investigate the presence of an immunoinflammatory reaction associated with advanced human diabetic macrovascular lesions. This may provide mechanistic insights in the pathogenesis of diabetic macrovasculopathy.
Conclusions
In summary, this semiquantitative study demonstrated that, histologically, atherosclerotic lesions from type 2 diabetic and nondiabetic patients share many features. Moreover, immunoinflammatory atherosclerotic features were also present in type 2 diabetes, as T cells and macrophages, as well as changes in the extracellular matrix component fibronectin, were observed. However, an increased amount of TNF-α was evident in type 2 diabetic lesions compared with nondiabetic lesions. This may
Acknowledgements
We are thankful to Dr. Marlene Rabinovitch and Dr. Jorge Luiz Gross for reviewing this manuscript and providing thoughtful comments. We also acknowledge the technical support form the Division of Pathology from the Hospital de Clı́nicas de Porto Alegre, especially the collaboration of Dr. Maria Izabel Edelweiss. We thank Mike Starr from The Hospital for Sick Children, University of Toronto, Canada, for performing the color photomicrographs. This study was supported by a grant to Dr. Clausell
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